Characterization of human CD30+ B cells and their relationship to Hodgkin and Reed-Sternberg cells of Hodgkin lymphoma

Small subsets of B cells in the germinal center (GC) and in extrafollicular regions of lymph nodes express the activation marker CD30. Very little is known about the specific features of these cells and their relationship to the CD30-expressing Hodgkin and Reed/Sternberg (HRS) cells of Hodgkin lymphoma. Phenotypic and immunoglobulin V gene analyses revealed that CD30+ GC B lymphocytes represent typical GC B cells, and that CD30+ non-GC B cells are mostly post-GC B cells. However, despite these seemingly distinct identities, both CD30+ subsets share an unexpectedly large overlap in specific transcriptome patterns, and are strikingly different from bulk GC B cells and classical memory and plasma cells, respectively. A main common feature of these CD30+ B cells is a strong MYC signature. CD30+ GC B cells appear to represent the recently described MYC+ GC B cell subset of recirculating centrocytes at the stage of centroblast transition. CD30+ non-GC B cells rather represent highly activated and proliferating memory B cells, differentiating into plasma cells. Notably, CD30+ B cells were more similar in their transcriptome patterns to HRS cells than any other B cell subset investigated, suggesting that HRS cells may either derive from CD30+ B cells or acquired a similar activation signature. In comparison to CD30+ B cells and other lymphomas, HRS cells show a remarkable downregulation of genes regulating cell cycle, genomic stability and polyploidity, providing a potential explanation for the genomic instability and multinuclearity of HRS cells.

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Weniger MA, Tiacci E, Schneider S, Arnolds J, Rüschenbaum S, Duppach J, Seifert M, Döring C, Hansmann ML, Küppers R